109 Pneumonia

Pneumonia is an acute inflammatory condition of lung parenchyma (lung tissue excluding the air­ways) caused by a variety of infectious agents and toxins and favored by aspects of the environment and/or the general physical status of the patient.

Several other pathogens (bacterial, viral, fungal, and parasitic) are recognized causative agents. The extent of the pulmonary involvement; the onset, pat­tern, and duration of symptoms; as well as the mor­tality rate depend on both the causative organism and precipitating factors. Chemical irritation, envi­ronmental exposure to noxious substances, or hyper­sensitivity can occasionally cause pneumonia. Aspi­ration pneumonia is a chemical-related condition, arising when vomited gastric acid is taken into the lung (along with oropharyngeal bacteria) by a pa­tient in a weakened or Semicomatose state induced by drugs, alcohol, anesthesia, or other disease.

In many cases, pneumonia is only one manifesta­tion of another specific disease such as the acquired immune deficiency syndrome (AIDS), ascariasis, cytomegalovirus, influenza, Legionnaire’s disease, plague, pneumocystis, Q fever, rickettsial diseases, tuberculosis, tularemia, and varicella.

Etiology and Epidemiology

Many pathogens have been associated with infec­tious pneumonia. Bacterial varieties include Escheri­chia coli, Hemophilus influenzae, Klebsiella pneu­moniae, Legionella pneumophila, Mycobacterium tuberculosis, staphylococci, and streptococci. Com­mon viral agents are arbovirus, cytomegalovirus, influenza, measles, respiratory syncytial virus, and varicella. Other pathogens include Mycoplasma pneumoniae, Blastomyces, Nocardia, Pneumocystis carinii, and the rickettsial pathogen Coxiella bur­netii. This list is far from exhaustive.

Despite the large number of pneumonia patho­gens, the disease develops only if other host or envi­ronmental conditions are met. Normally the airways and lung tissue distal to the throat (glottis) are ster­ile. Occasionally, organisms that are always present in the upper airway, in the digestive tract, or on the skin enter the lung. Ordinarily they are rapidly eliminated either by mechanical means, such as by coughing and the microscopic action of cilia, or by immune mechanisms. Infection and the resultant inflammation of pneumonia can occur in healthy individuals, but are often associated with a break­down in one or more of the usual defense mecha­nisms or, more rarely, with exposure to a particu­larly virulent strain of pathogen or an unusually high aerosol dose of organism (as in Legionnaire’s disease). Occasionally, bacterial pneumonia will oc­cur as a result of septicemic spread from an infec­tious focus elsewhere in the body.

Immune defenses are altered by underlying debil­ity, be it nutritional (starvation and alcoholism), in­fectious (tuberculosis and AIDS), neoplastic (cancer or lymphoma), or iatrogenic.

Mechanical defenses are hampered by immobility due to altered consciousness, paralysis or pain, endo­tracheal intubation, and prior viral infection of the upper airway, such as bronchitis or a cold. Contro­versy surrounds the ancient etiologic theory about cold temperatures. August Hirsch (1886) found a high incidence of pneumonia in months having wide variability in temperature. Two factors do tend to support an indirect correlation between cold and pneumonia: Predisposing viral infections are more common in winter, and some evidence suggests that the mechanical action of cilia is slowed on prolonged exposure to cold.

Lobar pneumonia appears in all populations. Its incidence and mortality rate are higher in individu­als or groups predisposed to one or more of the fac­tors described above. Elderly patients frequently de­velop pneumonia as the terminal complication of other debilitating illness, hence the famous meta­phor “friend of the aged” (Osler 1901).

Mortality rates for pneumonia are difficult to esti­mate because of its multifactorial nature and the fact that it can complicate other diseases. As men­tioned previously, untreated lobar pneumonia can result in death in 30 percent of cases. With antibiot­ics, fatalities are reduced to a varying extent depend­ing on the underlying condition of the patient, but in persons over the age of 12 years the mortality is at least 18 percent and in immunocompromised per­sons it is much higher.

Other forms of pneumonia follow epidemiological patterns that reflect the frequency of the organism or causative toxins in the host’s environment, as for example Legionella, which favors water in air­conditioning systems.

Clinical Manifestations

The incubation period for pneumonia is variable, de­pending on the causative organism, but pneumo­coccal pneumonia has a fairly uniform pattern. There may be a brief prodrome of coldlike symptoms, but usually the onset is sudden, with shaking chills and a rapid rise in temperature, followed by a rise in heart and respiratory rates. Cough productive of “rusty” blood-tinged sputum and dyspnea are usual. Most pa­tients experience pleuritic chest pain. In severe cases, there can be inadequate oxygenation of blood, lead­ing to cyanosis. If untreated, the fever and other symptoms persist for at least 7 to 10 days, when a “crisis” may occur consisting of sweating with de­fervescence and spontaneous resolution. With antibi­otic treatment, the fever usually falls within 48 hours. Untreated, or inadequately treated, the dis­ease may progress to dyspnea, shock, abscess forma­tion, empyema, and disseminated infection.

Diagnosis is based on the classic history and physi­cal findings. Dullness to percussion is detected over the involved lobe(s) of lung, and auscultation may reveal decreased air entry, crepitant rales, broncho­phony, whispering pectoriloquy, and variable alter­ation in fremitus, which reflects the pathological state of the lung tissue as it progresses through edema to consolidation and resolution or suppura­tion. Confirmation of the diagnosis is made by chest X-ray, and the specific pathogen is identified in spu­tum stains and culture. Treatment consists of rest, hydration, oxygen if necessary, and antibiotics. The selection of the last is based on, or endorsed by, the culture results.

In the nonlobar forms of pneumonia with diffuse inflammation, the history may be atypical and physi­cal examination unreliable. In these cases, chest X- ray and special cultures may be necessary. In some cases, the precise identity of the pathogen is con­firmed by serologic tests for specific and/or nonspe­cific antibodies (viral and mycoplasma pneumonia) or by immunofluorescence techniques {Legionella). When the patient is unable to cough or the inflamma­tion is nonpyogenic, lung biopsy for microscopic in­spection and culture is required (pneumocystis).

History

Antiquity Through the Eighteenth Century

Lobar pneumonia has probably always afflicted hu­mans. Pneumococcal organisms have been found in prehistoric remains, and evidence of the disease it­self has been observed in Egyptian mummies from 1200 B.C. (Ruffier 1921; Janssens 1970; Grmek 1983). Epidemics of this disease are probably less common than has previously been thought, however. In his pre-germ-theory observations, Hirsch cited sixteenth- to late-nineteenth-century reports of epi­demic outbreaks of “pneumonia” in numerous places on six continents. He emphasized that nearly all these records drew attention to “the malignant type of disease” and the “typhoid symptoms” (Hirsch 1886).

Pneumonia is not only an old disease, it is also one of the oldest diagnosed diseases. Hippocratic accounts of a highly lethal illness called peripleu- monin give a readily identifiable description of the symptoms, progression, and suppurative complica­tions of classic pneumonia and localize the disease to the lung. This disease was a paradigmatic exam­ple of the Greek theory that held that all illness progressed through coction (approximately, incuba­tion and early illness) to crisis and lysis (breaking up), while certain days in this sequence were “criti­cal” to the outcome (Sigerist 1951). These writers based the diagnosis on the symptoms, but the physi­cal sign of “clubbing” or “Hippocratic nails” was associated with prolonged pneumonia. Auscultation was also recommended to confirm the presence of pus in the chest. Variant pneumonic conditions of the lung were also described, including lethargy, moist and dry pneumonia, also called erysipelas of the lung. Therapy included bleeding, fluids, expecto­rants, and, only if absolutely necessary, surgical evacuation of empyemic pus (Hippocrates 1988; Pot­ter 1988).

In the first century A.D., Aretaeus of Cappadocia distinguished this disease from pleurisy, and four centuries later Caelius Aurelianus recognized that it could be confined to only certain parts of the lung. Except for a few subtle modifications, little change occurred in the clinical diagnosis and treatment of pneumonia until the early nineteenth century.

Nineteenth Through Twentieth Century

It is true that eighteenth-century pathological anato­mists drew attention to the microscopic appearance of the lung in fatal cases of lobar pneumonia. This work, however, had little impact on diagnosis until 1808, when Jean-Nicolas Corvisart translated and revised the 1761 treatise on percussion by Leopold Auenbrugger. This technique made it possible to detect and localize the presence of fluid or consolida­tion in the lung and to follow its evolution. Eight years later, Corvisarfs student, Rene Laennec, car­ried this one step further when he invented the stethoscope. In calling his technique “mediate aus­cultation,” Laennec readily gave priority to Hippoc­rates for having practiced the “immediate” variety by direct application of the ear to the chest. Laennec recommended both percussion and auscultation of the breath sounds and voice to confirm the physical diagnosis of pneumonia. With this combination he was able to distinguish consolidated lung from pleural fluid or pus in the living patient. He intro­duced most of the technical terms for pathological lung sounds - including “rale,” “rhoncus,” “crepita­tion,” “bronchophony,” “egophony” - some of which became pathognomonic for disease states. In addi­tion, he adopted Giovanni Morgagni’s notion of “hepatisation of the lung,” as a descriptive term for consolidation. Percussion and auscultation changed the concept of pneumonia from a definition based on classic symptoms to one based on classic physical findings. This conceptual shift was endorsed but not altered by the advent of the chest X-ray at the turn of this century.

The Italians Giovanni Rasori and Giacomo Thom- masini had recommended high-dose antimony potas­sium tartrate (tartar emetic) as a treatment for pneumonia, and Laennec used the new method of sta­tistical analysis with historical controls to suggest that this was an effective remedy. Yet in spite of its potential utility, the extreme toxicity of the drug guaranteed its unpopularity (Duffin 1985). Benjamin Rush, an American, and Laennec’s contemporary, Jean Baptiste Bouillaud, were proponents of copious “coup sur coup” phlebotomy. Until the late nine­teenth century, when salicylates became available for fever, pneumonia therapy consisted of various combinations and quantities of the ancient remedies, emetics, mercury, and especially bleeding (Risse 1986; Warner 1986).

Germ theory had a major impact on the concept of pneumonia, but it was rapidly apparent that despite its fairly homogeneous clinical manifestations this disease was associated not with a single germ (like tuberculosis and cholera) but with a variety of patho­gens. This situation cast some doubt on the imputed role of each new pathogen. In December 1880, Louis Pasteur isolated the organism that would later be­come the pneumococcus. Carl Friedlander discov­ered the first lung-derived pneumonia organism, K. pneumoniae (Friedlander’s bacillus) in 1883. Albert Frankel identified the pneumococcus (D. pneumo­niae) in 1884, and Anton Weichselbaum confirmed his findings in 1886. Klebsiella was found to be quite rare and seemed to favor the upper lobes, whereas the pneumococcus favored the lower lobes; however, there was some overlap between the pneumonic states induced by these organisms. Specific diagno­ses could be made only by isolation of the pathogen in culture.

Gradually many other organisms and viruses came to be associated with pneumonia, usually in clinical settings that deviated more or less from clas­sic lobar pneumonia. For example (and to name only a few), H. influenzae was isolated in 1918; Myco­plasma pneumoniae (the “Eaton agent” of “atypical pneumonia”) in 1944; L. pneumophila in 1977 (Hud­son 1979; Denny 1981; Stevens 1981; Levin 1984). It is likely that new pathogens will be recognized as antibiotics and vaccination alter the ecology of the lung.

Knowledge of the pneumococcus led to improve­ment in treatment and reduction in mortality from pneumonia, but it also had a major impact on the broad fields of immunology, bacteriology, and molecu­lar genetics. Study of the capsule - its antigenic prop­erties and capacity to transform - provided key infor­mation about drug resistance in bacteria: Acquired assistance of pneumococci was first recognized in 1912, long before the antibiotic era (Austrian 1981). Rufus Cole, Raymond Dochez, and Oswald Avery de­veloped typologies for the pneumococci before and during World War I, and in 1929 Rene Dubos discov­ered a bacterial enzyme that decomposed the capsu­lar polysaccharide of type HI pneumococcus, a discov­ery that contributed to the later work of Jacques Monod (Benison 1976).

Treatment and prevention of pneumonia have been dramatically improved in the twentieth century. Oxy­gen therapy was introduced by William C. Stadie dur­ing the 1918 New York influenza epidemic (Harvey 1979). Typing of pneumococci led to the 1912 intro­duction of antisera by Rufus Cole, who claimed that, by 1929, this therapy reduced mortality in some popu­lations to 10.5 percent (Dowling 1973). Antisera were effective only when the exact type of pneumococcus was known. Gerhard Domagk’s Pronotosil (sulfanila­mide) was not particularly effective against pneumo­coccus, but it did control other predisposing condi­tions. Its successor, sulfapyridine, was more effective. The advent of penicillin in the mid-1940s led to fur­ther reduction in mortality; however, it also led to the evolution of penicillin-resistant strains of pneumo­cocci and the now seemingly endless chase after effec­tive derivatives against so-called new organisms (Weinstein 1980).

Pneumonia control programs relied at first on antipneumococcal serum therapy, but as early as 1911, Almroth E. Wright conducted vaccination tri­als on thousands of black South African gold miners (Dowling 1973; Austrian 1981). These trials, con­ducted before the diversity of capsular types was fully appreciated, were inconclusive. It was not until 1945 that unequivocal demonstration of protection against type-specific pneumococcal infection in hu­mans was demonstrated by Colin M. MacLeod and Michael Heidelberger using a tetra valent vaccine. Contemporary vaccines contain at least 23 capsular antigens and are 80 to 90 percent effective in immunocompetent persons, but may be useless in some forms of immunodeficiency.

Jacalyn Duffin

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